The long-term objectives of this project are to characterize the metabolism and assess the potential toxic effects n humans of the benzenearsonate additives in poultry and swine feed. Such information would provide the basis for consideration of potential metabolic or disease impact in humans, upon ingestion of these compounds. The benzene-arsonates, arsanilic acid (4-aminobenzenearsonic acid) and roxarsone (4-hydroxy-3-nitrobenzenearsonic acid) are reactive compounds, with their phenolic aromatic amine, and aromatic nitro groups. Chronic exposure of humans to such compounds in the food supply is a matter of serious cancer, since structurally similar compounds are metabolized to active electrophiles which react with protein and DNA molecules to form tissue toxins or mutagens. Surprisingly, it appears that little attention has been given to analyzing human biotransformation of benzenearsonate compounds from consumed meat. An expanded study of the study of the action of human enzymes in biotransformations of the benzenearsonates will be undertaken, using human liver, including microsomes, the post-mitochondrial S9 fraction, several individual cytochrome P450 isoforms, flavin monoozygenases (FMO), and human cells in culture. Additional studies of the inhibitor roles of these benzenearsonates will be pursued as well, with attention given to the acid and alkaline phosphatase systems in human cell culture. Protein tyrosine phosphatases (PTPases) will also be investigated as benzenearsonate inhibition targets. The PTPases occur as both cytoplasmic and integral membrane enzymes with cell growth inhibition and tumor suppression characteristics.